Background: The 16q23.1 tumor suppressor gene (TSG) of ADAMTS18 has been identified to be aberrant methylated in clear cell renal cell carcinoma (ccRCC), and there still exists an unclear situation between its methylation and the progression of ccRCC.
Objective: To analyze the biological function and mechanism of ADAMTS18 gene in the tumorigenesis and progression of ccRCC.
Methods: We examined ADAMTS18 gene methylation using methylation- specific polymerase chain reaction (MSP) in 92 ccRCC primary tumors from September 2017 to May 2018. Using reverse transcriptase PCR (RT-PCR) and immunohistochemical (IHC) assay, the relative expression level of ADAMTS18 was measured in the representative tumor samples with their adjacent normal tissues. Meanwhile, colony formation, cell viability, wound healing, transwell chamber, flow cytometry, and PI staining were performed to confirm the tumor-suppressive function and mechanism of ADAMTS18 gene.
Results: Aberrant methylation was further detected in 47 of the 92 (51.1%) primary tumors and in 8 of the 92 (8.7%) adjacent normal tissues (p < 0.05). Due to the phenomenon of aberrant methylation, ectopic low-level expression of ADAMTS18 gene could result in the promotion of tumorigenesis and progression in ccRCC.
Conclusion: The aberrantly methylated ADAMTS18 gene may be involved in the tumorigenesis and progression of ccRCC.
Keywords: ADAMTS18 gene; Clear cell renal cell carcinoma; Methylation; Tumor suppressor gene.